RIC1

Chr 9AR

RIC1 partner of RAB6A GEF complex

Also known as: CATIFA, CIP150, KIAA1432, bA207C16.1

The RIC1 protein forms a guanine nucleotide exchange factor complex that activates RAB6A to facilitate endosome-to-Golgi vesicle fusion and is required for procollagen transport, secretion, and craniofacial skeletal development. Biallelic mutations cause CATIFA syndrome, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.398), indicating that complete loss of function is likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.401 OMIM phenotype
Clinical SummaryRIC1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
96 unique Pathogenic / Likely Pathogenic· 85 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.001
Z-score 5.85
OE 0.28 (0.200.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.07Z-score
OE missense 0.99 (0.931.05)
747 obs / 752.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.200.40)
00.351.4
Missense OE0.99 (0.931.05)
00.61.4
Synonymous OE1.41
01.21.6
LoF obs/exp: 21 / 76.1Missense obs/exp: 747 / 752.7Syn Z: -5.29
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedRIC1-related syndromic congenital cataractOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4090th %ile
GOF
0.3491th %ile
LOF
0.66top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic94
Likely Pathogenic2
VUS85
Likely Benign11
Benign7
Conflicting1
94
Pathogenic
2
Likely Pathogenic
85
VUS
11
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
94
0
94
Likely Pathogenic
0
0
2
0
2
VUS
3
76
5
1
85
Likely Benign
0
6
0
5
11
Benign
0
0
3
4
7
Conflicting
1
Total38210410200

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RIC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC